The main goal of this paper is to compare single- and two-phase modeling approaches for forced convection flow of water/TiO2 nanofluid. The considered geometry is a horizontal tube with constant wall heat flux boundary condition where flow regime is turbulent. A computational fluid dynamics (CFD) approach is utilized for heat transfer and flow field estimation of the single-phase and three different two-phase approaches, namely, volume of fluid, mixture, and Eulerian models. Results are presented for Reynolds numbers ranging from 9000 to 21,000, for different nanoparticle diameters ranging from 20 to 40nm, and for values of volume fractions ranging from 0 to 4%. The obtained results show that the values of entropy generation for thermal and turbulent dissipation are very close for the single-phase and mixture models. Numerical investigation showed that the values of entropy production for pure water are identical regardless of the CFD approach; however, when the volume fraction of nanoparticles increases, differences between the models appear.